PAXX and its paralogs synergistically direct DNA polymerase λ activity in DNA repair

Craxton, A., Munnur, D., Jukes-Jones, R., Skalka, G., Langlais, C., Cain, K. and Malewicz, M. (2018) PAXX and its paralogs synergistically direct DNA polymerase λ activity in DNA repair. Nature Communications, 9, 3877. (doi: 10.1038/s41467-018-06127-y) (PMID:30250067) (PMCID:PMC6155126)

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Abstract

PAXX is a recently identified component of the nonhomologous end joining (NHEJ) DNA repair pathway. The molecular mechanisms of PAXX action remain largely unclear. Here we characterise the interactomes of PAXX and its paralogs, XLF and XRCC4, to show that these factors share the ability to interact with DNA polymerase λ (Pol λ), stimulate its activity and are required for recruitment of Pol λ to laser-induced DNA damage sites. Stimulation of Pol λ activity by XRCC4 paralogs requires a direct interaction between the SP/8 kDa domain of Pol λ and their N-terminal head domains to facilitate recognition of the 5′ end of substrate gaps. Furthermore, PAXX and XLF collaborate with Pol λ to promote joining of incompatible DNA ends and are redundant in supporting Pol λ function in vivo. Our findings identify Pol λ as a novel downstream effector of PAXX function and show XRCC4 paralogs act in synergy to regulate polymerase activity in NHEJ.

Item Type:Articles
Additional Information:This work was supported by the Medical Research Council (MRC) UK.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Skalka, Dr George
Authors: Craxton, A., Munnur, D., Jukes-Jones, R., Skalka, G., Langlais, C., Cain, K., and Malewicz, M.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature Research
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9: 3877
Publisher Policy:Reproduced under a Creative Commons License

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